The main objective of this program is to perform epidemiological, clinical and immunological studies to expand our knowledge of the pathogenesis, treatment and control of schistosomiasis, leishmaniasis and persistent diarrheal disease. The UFBA/UFC/UFRN/FIOCRUZ TROPICAL MEDICINE RESEARCH CENTER Consortium will bring together the expertise of investigators from the Northeast of Brazil. The TMRC will increase our collaboration with American scientists and will provide opportunities for United States investigators to conduct research on tropical disease. Major diseases which are endemic in the impoverished Northeast of Brazil include: leishmaniasis, schistosomiasis, filariasis, Chagas' disease, leprosy, malaria, diarrhea due to enteric infections and helminthiasis. The overall programmatic theme is the role of cytokines in pathogenesis and disease expression and novel approaches to treatment and control of schistosomiasis, leishmaniasis and persistent diarrhea. Project I. "S.mansoni: Hepatosplenism, HLA and T cell responses" will determine the influence of HLA class II alleles on the development of cellular immune responses to crude and defined schistosoma antigens that led to the development of severe hepatosplenism schistosomiasis. Project II. "Natural history and human immunogenetics of visceral leishmaniasis in Ceara and Rio Grande do Norte, Brazil" will characterize immunological and genetic factors associated with resistance or susceptibility to the development of visceral leishmaniasis. Project III. "Immunoregulation in leishmaniasis" will determine immunological events occurring early after the contact of leishmania with macrophages, the role of cytokines (GM-CSF and IL-12) as vaccine adjuvants and the immunological and clinical responses related to treatment of cutaneous leishmaniasis with IL-12 in combination with pentavalent antimony. Project IV. "Role of Cytokines, Cellular Immunologic Determinants and New Approaches to Treating Persistent diarrhea in population at high risk for Crytosporidium, enteroaggregative E. coli and other enteric infections" will define the role of enteric cytokines and cellular immunity in the physiologic derangements in persistent cryptosporidal, E. coli and other diarrhea illnesses and to examine novel, function-based approaches to their therapy.